Scenario 1 - Part 1:
A 24-year-old man was seen at the outpatient clinic because of persistent hypophosphatemia.
The patient had been previously well until two years ago, when he developed a hip fracture upon falling downstairs. After which, he suffered generalised bony pains for the subsequent two years.
Laboratory investigations performed at time of hip fracture are shown in table I
Test |
2 years ago |
S. Creatinine |
0.9 mg/dL |
serum Calcium |
9.3 mg/dL |
serum Phosphorus |
1.3 mg/dL |
serum PTH |
53 pg/mL |
serum potassium |
4 mg/dl |
uric acid |
6 mg/dl |
25-hydroxy vit-D |
10 ng/ml (33-100) |
Alk-phosphatase/total |
170 U/L (30-130) |
Alk-Phosphatase/bone specific |
50 (7.5-25) |
Urinary Phosphorus |
0.6 (<0.1 g/day) |
A- Interpret the above laboratory investigations.
B- Discuss the main mechanisms leading to hypophosphatemia.
C- What is the most likely mechanism in this case.
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A – symptomatic hypophosphataemia causing symptoms
B – redistribution from ECF to ICF 2/ decreased absorption from gut / increase urinary phosphate
C primary renal phosphate wasting
A-hypophosphatemia
excess urinary phosphate excretion
vitamin D deficiency
normal PTH
normal s.K and uric acid
B-renal wasting and decrease intestinal absorption
C renal loss but other than Fanconi syndrome
A- Interpret the above laboratory investigations.
B- Discuss the main mechanisms leading to hypophosphatemia.
Internal redistribution
Decreased intestinal absorption
Increased urinary excretion
Removal by kidney replacement therapies
C- What is the most likely mechanism in this case. Increased urinary excretion as result of Vitamin D deficiency
A- Interpret the above laboratory investigations.Hypophosphatemia , elevated ALP, high phosphaturia and hypo vitamin D
B- Discuss the main mechanisms leading to hypophosphatemia.
C- What is the most likely mechanism in this case.Vitamin D deficiency and renal loss
A-hypophosphatemia with high phosphaturia and hypo vitamin D
B- 1- renal wasting (high FGF23)
2- decrease intestinal absorption (decrease VD)
C renal loss but other than Fanconi syndrome
A- Interpret the above laboratory investigations.
B- Discuss the main mechanisms leading to hypophosphatemia.
C- What is the most likely mechanism in this case. Vitamin D deficiency .
A- Interpret the above laboratory investigations.
Young patient with no PMHx has hypophosphatemia most likely due to hyperphosphaturia or hypovitaminosis.
B- Discuss the main mechanisms leading to hypophosphatemia.Most likely the patient has high FGF 23 causing high phosphate loss through kidney and that lead to hypophosphatemia.
C- What is the most likely mechanism in this case.
Hyperphosphaturia in this young patient case, most likely due to tumor induced osteomalacia.
Could you interpret the above laboratory investigations?This patient’s lab showed severe hypophosphatemia with normal calcium, low Vit D levels, and high SBALP and phosphate excretion.
The above pictures may denote hypophosphatemia, rickets or osteomalacia, and Fanconi syndrome.
Discuss the main mechanisms leading to hypophosphatemia.Either increase excretion or decrease absorption from the intestine.
INCREASE phosphate excretion like in the case of CKD or TIO, WHERE tumors release FGF23, which is the phosphaturia hormone.
What is the most likely mechanism in this case.most likely, this patient has renal cause of hypophosphatemia, which is evidenced by high phosphate excretion in the kidney and low Vit D along with bone pain and hip fractuers.
Thankyou dear colleagues
A. Interpret the above laboratory investigations.
The previous laboratory investigations show hypophosphatemia. Moreover, hypovitaminosis D and increased urinary phosphorus excretion may contribute to hypophosphatemia. Normal serum potassium and uric acid could be helpful in exclusion of fanconi syndrome that is associated with multiple abnormalities in proximal tubule reabsorption like hypouricemia, aminoaciduria and proximal RTA. On the other hand, normal PTH level and high total alkaline phosphatase.
Hypophosphatemia is mostly the cause of the patient’s symptoms and presentation which are muscle weakness,fatigue, bone pain and non traumatic fractures.
B. Discuss the main mechanisms leading to hypophosphatemia.
Major mechanisms that lead to hypophosphatemia are:
C. What is the most likely mechanism in this case
Increased urinary phosphorus excretion more than 100 mg /day, low level of vitamin D, persistent bone pain and skeletal fracture suggest a renal cause of hypophosphatemia. Excess production of the phosphaturic hormone FGF23 either due to hereditary forms of hypophosphatemic rickets and oncogenic osteomalacia. Inactivating mutations in the PHEX gene (in bone tissue) cause X linked hypophosphatemia by increasing production, through an unknown mechanism, of FGF 23 which in turn, acts as a counterregulatory hormone to inhibit phosphate reabsorption by sodium/phosphate cotransporters in the proximal renal tubules. Tubular defect as Fanconi syndrome could be excluded because absent other associated abnormalities in proximal tubule reabsorption like hypokalemia and hypouricemia.
Interpret the above laboratory investigations.
II.Discuss the main mechanisms leading to hypophosphatemia.
renal phosphate wasting
DD:
III.What is the most likely mechanism in this case.
Genetic hypophosphatemic rickets:
normocalsemia, hypophosphatemia, hyperuricemia, hyperphosphaturia, and elevated uric acid. No clue about Fanconi, like hyperuricosuria, glycosuria, metabolic acidosis, etc., most probably due to a deficiency in vitamin D as shown by measurement and mild elevation of PTH, which I can expect to be higher. Renal phosphorous wasting could be due to vitamin D deficiency
A- Interpret the above laboratory investigations.
Normal calcium
Low phosphate
Normal PTH
Slightly high ALP
High urinary pi
Normal RFT
Normal electrolytes
Low vitamin D3
B- Discuss the main mechanisms leading to hypophosphatemia.
Vitamin D3 deficiency
Genetic renal ricket
Fanconi syndrome
Oncogenic osteomalacia
C- What is the most likely mechanism in this case.
As there’s low serum pi and high 24 hrs urinary pi , so this is a renal pi loss.
Mostly this case is genetic hypophosphatemic ricket either Xlinked, AD, AR .
Interpret the above laboratory investigations.
Discuss the main mechanisms leading to hypophosphatemia.
What is the most likely mechanism in this case.
A- Interpret the above laboratory investigations.normal kidney function ,PTH and calcium
total and bone specific ALP is elevated .
hypovitaminosis D and significant urinary phosphate excretion.
B- Discuss the main mechanisms leading to hypophosphatemia.there are several mechanisms that can lead to hypophosphatemia including
vitamin d deficiency, low GI phosphate absorption , hyperparathyroidism, DKA treatment , TUMOURs.increases renal loss .starvation.TPN
C- What is the most likely mechanism in this case.the most likely mechanism is vitamin D deficiency.
A- Interpret the above laboratory investigations.
B- Discuss the main mechanisms leading to hypophosphatemia.
C- What is the most likely mechanism in this case.
Interpret the above laboratory investigations.the patient has hyposphatemia, low vit D level, normal serum creatinine, and serum calcium level, high PTH and high bone specific alkaline phosphatase
all these results point to vit D DEFICIENCY causing hypophosphatemia, 2ry hyperparathyroidism, which makes serum calcium normal due to increases bone resorption
Discuss the main mechanisms leading to hypophosphatemia.Mechanism of hypophosphatemia
1- Intracellular shift as in acute respiratory alkalosis, during ttt of DKA, during refeeding
2- Decreased GIT absorption:
a- inadequate intake uncommon cause unless it is prolonged as kidney compensates by decreasing phosphate excretion,
b- medications: phosphate binders
3- Increase phosphate excreation:
a-hyperparathyroidism,
b- vit D deficiency
c- primary renal wasting: i-x-linked hypophosphatemic ricket, which occurs due to mutation of PHEX GENE rendering FGF-23 resistant to cleavage, ii- tumor induced osteomalacia, iii- Fanconi syndrome
What is the most likely mechanism in this casevit D deficiency
A- Interpret the above laboratory investigations.
Hypophosphatemia normal level calcium elevated level of alkaline phosphatase and bone specific alkaline phosphatase and hypovitaminosis d with increase po4 excretion .
B- Discuss the main mechanisms leading to hypophosphatemia.
Hypophosphatemia in these case mostly due to renal loss associated with hypovitaminosis d but in general the low po4 mostly due to
Decreased GIT absorption inadequate phosphate intake, malabsorption,sever starvation, vitamin d deficiency, phosphate binders.
Increased phosphate loss hyperparathyroidism, vitamin d deficiency, tumour induced osteomalacia, genetic diseases, falconi syndrome, post renal transplantation, imatinib
Shift from extracellular phosphate into the intracellular space refeeding syndrome, hungry bone syndrome,acute respiratory alkalosis, during txt of DKA
C- What is the most likely mechanism in this case.
Mostly dueto hypophosphatemia secondary to Vitamin d deficiency
good job dr Rabab
THIS PATIENT HAS HYPOPHOSPATEMIA WITH ELEVATED ALK. PHOSPHATASE BUT WITH NORMAL KFT , NORMAL PTH AND CALCIUM, SO HYPERPARATHYROIEDISM EXCLUDED, BUT HE HAS VERY LOW VITAMIN D AND INCREASED URINARY EXCRETION OF PHOSPHOROUS
VIT D DEFICIENCY IS THE MOST LIKLY MECHANISM IN THIS PATIENT , BUT DIFFERENTIAL DIAGNOSIS INCLUDING SOME GENETIC DEFECTS, TUBULAR DESFUNCTION OR CHRONIC ALCOHOL ABUSE
I. Interpret the above laboratory investigations.
II.Discuss the main mechanisms leading to hypophosphatemia.
–Low serum phosphate and high 24 urine Pi indicates renal phosphate wasting, and the differential diagnosis are:
III.What is the most likely mechanism in this case.
Very good dr Ben
A- Interpret the above laboratory investigations.
The patient has hypophosphamia, vitamin D deficiency, elevated alkaline phosphotase, normal electrolytes, elevated urinary phosphorous
B- Discuss the main mechanisms leading to hypophosphatemia.
1. Trancellular shift like use of insulin, hungery bone disease
2. Reduce intake nutritional
3.renal loss eg x linked hypophosphametic ricket, hyperparathyroidism, fanconi syndrome
4.multifactorial eg vitamin D deficiency, vitamin D dependant ricket type 1and 2
C- What is the most likely mechanism in this case.
Vitamin D deficiency and renal loss
A- Interpret the above laboratory investigations.Normal serum creatinine,serum calcium, serum uric acid, serum potassium, PTH
Hypophosphatemia with high urinary phosphorus excretion
high levels of ALP and B-ALP
B- Discuss the main mechanisms leading to hypophosphatemia.Hypophosphatemia is most commonly induced by one of three causes:
C- What is the most likely mechanism in this case.Primary renal phosphate wasting — There are several rare syndromes characterized by isolated renal phosphate wasting.
1-In X-linked hypophosphatemic rickets (which had been called vitamin D-resistant rickets), the defect in proximal tubular phosphate transport is due to a mutation in the PHEX gene. This gene encodes an endopeptidase that indirectly alters the degradation and production of FGF-23, a phosphatonin that promotes urinary phosphate excretion and suppresses calcitriol synthesis.
2-autosomal dominant hypophosphatemic rickets and results from mutations in the FGF-23 gene on chromosome 12p13. This mutant form of FGF-23 is resistant to protease cleavage but retains its phosphaturic properties
Tumor-induced osteomalacia. These patients usually have tumors of mesenchymal origin, often a sclerosing type of hemangiopericytoma, that produce a phosphaturic hormone(s) ( FGF-23, MEPE, and sFRP-4)
Excellent dr Alaa
A. Vitamin D deficiency, hypophosphatemia due to increased phosphaturia, high alk. phosphate esp. Bone AP.
B. Main mechanism is the Decreased intestinal absorption of phosphat due to Vitamin D deficiency and increased renal secretion of phosphat like fanconi diseasea or decreased expression of natrium phosphate cotransporters 2a and 2c in PCT.
Hypophosphatemia can be also caused by refeeding syndrom.use of certain diuretics and antacids.
C.most likely is a osteomalacia by vitamin D deficiency due to high fgf23 level what explain phosphate wasting in this patient
There is forms of heredital vitamin d resistant hypophosphatemic osteomalacia that related to high fgf23 level
A- Interpret the above laboratory investigations.
This patient has hyperphosphaturia leading to hypophosphatemia, likely due to vitamin D deficiency.
B- Discuss the main mechanisms leading to hypophosphatemia.
Hypophosphatemia may can result from:
· Internal redistribution
o Refeeding
o Hungry bone syndrome
· Decreased absiorption
o Inadequate intake
o Chronic diarrhea
· Renal loss
o Hyperparathyroidism
o Fanconi syndrome
o Vitamin D defeciency
C- What is the most likely mechanism in this case.
Most likely, vitamin deficiency
A- Interpret the above laboratory investigations.
Hypophosphatemia-High urinary phosphate-Low vitamin D- High ALP, BSAP
B- Discuss the main mechanisms leading to hypophosphatemia
Redistribution such as refeeding
Increase Urinary loss of phosphate such as hyperparathyroidism, Impaired vitamin D metabolism
Reduced intake such as Malnutrition or vitamin D deficiency
Cellular shifts such as acute respiratory alkalosis
C- What is the most likely mechanism in this case.
Most likely due to osteomalacia caused by vitamin D deficiency
A- Interpret the above laboratory investigationshypophosphatemia ,hypovitaminosis D ,high alkaline phosphatase ,and high PTH with increase urinary phosphate excretion and normal kidney function
B- Discuss the main mechanisms leading to hypophosphatemia.Three primary mechanisms of hypophosphatemia exist: increased renal excretion, decreased intestinal absorption, and movement of phosphate from the extracellular to intracellular compartments.
C- What is the most likely mechanism in this case.osteomalcia dt vitamin d deficiency
A- Interpret the above laboratory investigations. normal renal function
Very low serum phosphorus with high urinary phosphorus level
low vitamin D moderately high alkaline phosphatase and high BSAP. Normal renal function and serum calcium with low vitamin D
B- Discuss the main mechanisms leading to hypophosphatemia.
Increased urinary phosphate excretion mostly due to high serum FGF 23 level
FGF 23 induced low level of active vitamin d with subsequent decreased intestinal absorption of phosphate
C- What is the most likely mechanism in this case
1- May be there is underlying Oncogenic Osteomalacia induced excess FGF23 secretion which causes excess po4 urinary secretion through decreased expression of the sodium-phosphate cotransporter in the proximal tubules of the kidney.2- vit. D resistant osteomalacia Hypophosphatemia cause low mineralization of the bone matrix,.3- Autosomal Recessive Hypophosphatemic Rickets (ARHPR),
4- Autosomal Dominant Hypophosphatemic Rickets (ADHPR) and
X-Linked Dominant Hypophosphatemic Rickets (XLHPR
A- Interpret the above laboratory investigations. normal renal function
Low phosphorus
high urinary phosphorus
low vitamin D
high alkaline phosphatase
high BSAP.
B- Discuss the main mechanisms leading to hypophosphatemia.
Redistribution of phosphate from the extracellular fluid into cells
Decreased intestinal absorption of phosphate
Increased urinary phosphate excretion
internal redistribution as refeeding syndrome, acute respiratory alkalosis . decreased intestinal absorption as chronic antacid therapy, steatorrhe.
C- What is the most likely mechanism in this casehypophosphatemia vit. D resistant osteomalacia
Hypophosphatemia cause low mineralization of the bone matrix, softening the bone and leading to osteomalacia.
the laboratory investigation revealed
– normal kidney function normal k level
-normocalcemia normal uric acid
-hypophosphatemia . assosited w phosphaturia
-hypovit D
-ALK -total and bone sp. ALK Hight
-PTH normal
THE IMPRESSION
Hypophosphatemia bone disease
this is seen most common in osteomalacia due to
vit. D deficiency , long term antacid abuse , hereditary phosphate wasting syndromes ( or hereditary hypophosphatemia rickets) ,malnutrion and tumor – induced osteomalacia
In addition Adult onset hypophosphatemia vit. D resistant osteomalacia is agroup of diseases characterized mainly by poor bone mineralization . osteomalacia or rickets( caused by hypophosphatemia ) and insufficient active vit. D production
### Hypothesis of FGF23 IS involved
A- Interpret the above laboratory investigations.Adult patient with normal renal function Low serum phosphorus, low vitamin D, high alkaline phosphatase, high phosphate excretion, and BSAP. normal calcium and PTH
Adult-onset hypophosphatemic osteomalacia
B- Discuss the main mechanisms leading to hypophosphatemia.
FGF-23 is associated with the onset of hypophosphatemic osteomalacia; it is a known phosphorus-regulating factor, with a normal level of ~10–50 ng/l.In addition, an increase in FGF-23 concentrations may inhibit the production and activity of 1-α hydroxylase, thereby reducing the production of 1,25-(OH)2D3 and phosphorus.
What is the most likely mechanism in this case?
Adult-onset hypophosphatemic vitamin D-resistant osteomalacia (AHVDRO) is a group of diseases characterized mainly by poor bone mineralization, osteomalacia or rickets (caused by hypophosphatemia), and insufficient active vitamin D production. There are three forms of AHVDRO: X-linked hypophosphatemic rickets/osteomalacia (XLH), autosomal dominant hypophosphatemic rickets (ADHR), and tumor-induced osteomalacia (TIO). Previous studies have investigated other factors that may contribute to the development of hypophosphatemia-associated osteomalacias, such as vitamin D receptor resistance.
Hypophosphatemia can cause inadequate mineralization of the bone matrix, subsequently softening the bone and leading to osteomalacia.
Genetic disorders that cause phosphate wasting include the following: